║่⃭ᛶヨ㦂௦᭰ἲࡢホ౯ሗ࿌᭩In vitro ▷᫬㛫᭚㟢ἲ
㸦Short Time Exposure In Vitro Test Method: STE ἲ㸧║่⃭ᛶ௦᭰ἲ㈨ᩱ⦅⧩ጤဨ఍

2015 ᖺ 9 ᭶ 29 ᪥17║่⃭ᛶ௦᭰ἲ㈨ᩱ⦅⧩ጤဨ఍➉ෆ ᑠⱑ 㸦P&G ࢖ࣀ࣮࣋ࢩࣙࣥྜྠ఍♫㸧ᑠᆏ ᛅྖ 㸦୍⯡㈈ᅋἲே ṧ␃㎰⸆◊✲ᡤ㸧బࠎᮌ ṇ἞ 㸦࢔ࢵࣦ࢕ྜྠ఍♫㸧᳃ᮧ ᬛ⨾ 㸦୍⯡㈈ᅋἲே 㣗ရ⸆ရᏳ඲ࢭࣥࢱ࣮㸧ྜྷᮧ ຌ 㸦ᮾி⌮⛉኱Ꮫྡ㄃ᩍᤵ㸧28␎ㄒ
AD: Applicable Domain
BCOP: Bovine Corneal Opacity and Permeability
CAS: Chemical Abstracts Services
CM: Cytosensor Microphysiometer
DMSO: Dimethyl Sulfoxide
ETDA: Ethylenediaminetetraacetic Acid
FL: Fluorescein Leakage
GHS: Globally Harmonized System of Classification and Labeling of ChemicalsICCVAM: Interagency Coordinating Committee on the Validation of Alternative Methods
ICE: Isolated Chicken Eye
JaCVAM: Japanese Center for the Validation of Alternative Methods
kPa: kiloPascals
MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
NICEATM: National Toxicology Program (NTP) Interagency Center for the Evaluation ofAlternative Toxicological Methods
OD: Optical Density
OECD: Organization for Economic Co-operation and Development
SD: Standard Deviation
SRD: Summary Review Document
SIRC: Statens Seruminstitut Rabbit Cornea
SLS: Sodium Lauryl Sulfate
STE: Short Time Exposure In Vitro Test
TG: Test Guideline
UN: United Nations

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せ᪨in vitro ▷᫬㛫᭚㟢ἲ㸦Short Time Exposure In Vitro Test Method㸸STE ἲ㸧ࡣࠊ࢘ࢧࢠ⏤᮶ࡢゅ⭷ୖ⓶⣽⬊࡟ᑐࡍࡿ໬Ꮫ≀㉁ࡢ⣽⬊ẘᛶࢆᣦᶆ࡟⏝࠸࡚║่⃭ᛶࢆホ౯ࡍࡿヨ㦂ἲ࡛࠶ࡿࠋࢺࢵࣉࢲ࢘ࣥ᪉ᘧ࡟࠾࠸࡚ UN GHS ༊ศ 1 ≀㉁ࢆ᳨ฟࡍࡿ᪉ἲࠊ࠾ࡼࡧ࣎ࢺ
࣒࢔ࢵࣉ᪉ᘧ࡟࠾࠸࡚ UN GHS ༊ศእ≀㉁ࢆ᳨ฟࡍࡿ᪉ἲ࡜ࡋ࡚ࣂࣜࢹ࣮ࢩࣙࣥࡀ⾜ࢃࢀࠊ2015 ᖺ࡟ OECD ࡢࢸࢫࢺ࢞࢖ࢻࣛ࢖ࣥ TG 491 ࡜ࡋ࡚᥇ᢥࡉࢀࡓࠋᮏሗ࿌᭩ࡣࠊICCVAM/NICEATM ࡢ SRD ࡸⓎ⾲ㄽᩥ࡞࡝ࢆࡶ࡜࡟ࠊ
᥇ᢥࡉࢀࡓ STE ἲࡢᴫせࢆㄝ᫂ࡋࠊJaCVAM ║่⃭ᛶ௦᭰ἲ㈨ᩱ⦅⧩ጤဨ఍ࡢពぢࢆ㏙࡭ࡓࡶࡢ࡛࠶ࡿࠋ ࢘ࢧࢠࢆ⏝࠸ࡓ Draize ║่⃭ᛶヨ㦂࡜ẚ㍑ࡋࡓ࡜ࡁࠊSTE ἲࡢࢺࢵࣉࢲ࢘ࣥ᪉ᘧ࠾ࡼࡧ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡟࠾ࡅࡿ୍⮴ᗘࡣ 83.2%࠾ࡼࡧ 84.6%ࠊഇ㝧ᛶ⋡ࡣ 1.2%࠾ࡼࡧ 19.3%ࠊ
ഇ㝜ᛶ⋡ࡣ 51.3%࠾ࡼࡧ 12.3%࡛࠶ࡗࡓࠋ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡟࠾࠸࡚㐺⏝㝖እ≀㉁ࢆ㝖࠸ࡓሙྜࡣࠊ୍⮴ᗘࠊഇ㝧ᛶ⋡ࠊഇ㝜ᛶ⋡ࡀ 90.2%ࠊ18.8%ࠊ1.9%࡛࠶ࡗࡓࠋ᪋タෆ࣭᪋タ㛫෌⌧ᛶࠊᢏ⾡⛣㌿ᛶ࡟㛵ࡋ࡚ࡣࠊᠱᛕࡉࢀࡿ⤖ᯝࡀ࡞࠿ࡗࡓࠋ
TG 491 ࡟‽ᣐࡋ࡚ᐇ᪋ࡍࢀࡤࠊSTE ἲࡣࢺࢵࣉࢲ࢘ࣥ᪉ᘧ࡛ UN GHS ༊ศ 1 ≀㉁ࢆ᳨ฟࡍࡿ᪉ἲࠊ࠾ࡼࡧ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡛ UN GHS ༊ศእ≀㉁ࢆ᳨ฟࡍࡿ᪉ἲ࡜ࡋ࡚⏝࠸ࡿࡇ࡜ࡀ࡛ࡁࡿ࡜ᮏጤဨ఍ࡣ⪃࠼ࡿࠋ

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1. ࡲ࠼࠾ࡁ໬Ꮫ≀㉁ࡢ║่⃭ᛶࢆホ౯ࡍࡿ᪉ἲ࡜ࡋ࡚ࡣࠊ࢘ࢧࢠࡢ║ࢆ⏝࠸ࡓ Draize ║่⃭ᛶヨ㦂ࡀᚑ᮶౑⏝ࡉࢀ࡚ࡁࡓࠋࡋ࠿ࡋࠊ㏆ᖺࡢື≀⚟♴࡟ᑐࡍࡿ㛵ᚰࡢ㧗ࡲࡾࡸḢᕞ࡟࠾ࡅࡿἲつไᨵṇ࡟ࡼࡾࠊࡑࡢ௦᭰ἲࡢ㛤Ⓨࡀ㐍ࡵࡽࢀ࣭ࣂࣜࢹ࣮ࢩࣙࣥࡀ⾜ࢃࢀ࡚ࡁࡓࠋ⌧ᅾ OECD ࡟ࡼࡾࢸࢫࢺ࢞࢖ࢻࣛ࢖ࣥ࡜ࡋ࡚᥇ᢥࡉࢀࡓ௦᭰ἲࡣࠊ࢘ࢩ᦬ฟゅ⭷ࡢΰ⃮
࠾ࡼࡧ㏱㐣ᛶヨ㦂㸦BCOP ἲࠊTG 437㸧ࠊࢽ࣡ࢺࣜ᦬ฟ║⌫ࢆ⏝࠸ࡓ║่⃭ᛶヨ㦂ἲ㸦ICE
ἲࠊTG 438㸧ࠊ࠾ࡼࡧࣇࣝ࢜ࣞࢭ࢖ࣥ₃ฟヨ㦂ἲ㸦FL ἲࠊTG 460㸧ࡢ 3 ヨ㦂ἲ࡛࠶ࡿࠋBCOP ἲ࡜ ICE ἲࡣ㣗⏝࡞࡝ࡢ┠ⓗ࡛ฎศࡉࢀࡓື≀ࡼࡾ᦬ฟࡋࡓჾᐁ࣭⤌⧊ࢆ⏝࠸࡚໬Ꮫ≀㉁ࡢ᭚㟢࡟ࡼࡾ⏕ࡌࡿゅ⭷ࡢ≀⌮ⓗ≉ᛶࡢኚ໬ࢆᣦᶆ࡟║่⃭ᛶࢆホ౯ࡍࡿヨ㦂ἲ࡛ࠊࢺࢵࣉࢲ࢘ࣥ᪉ᘧ࡟࠾࠸࡚㔜⠜࡞║ࡢയᐖࢆ㉳ࡇࡍ㸦ࡍ࡞ࢃࡕࠊUN GHS ༊ศ 1㸧≀㉁ࢆ᳨ฟࡍࡿ᪉ἲ࡜ࡋ࡚ࠊࡲࡓ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡟࠾࠸࡚║࡟ᑐࡍࡿ㔜⠜࡞ᦆയᛶࢆ᭷ࡍࡿ≀㉁࠾ࡼࡧ║่⃭ᛶ≀㉁࡜ࡣศ㢮ࡉࢀ࡞࠸㸦ࡍ࡞ࢃࡕࠊUN GHS ༊ศእ㸧≀㉁ࢆ
᳨ฟࡍࡿ᪉ἲ࡜ࡋ࡚⏝࠸ࡽࢀࡿࠋFL ἲࡣ༢ᒙᇵ㣴ࡋࡓᒀ⣽⟶ୖ⓶⣽⬊ࢆ⏝࠸࡚໬Ꮫ≀㉁ࡢ᭚㟢࡟ࡼࡾ⏕ࡌࡿ⣽⬊㛫⤖ྜࡢയᐖࢆᣦᶆ࡟║่⃭ᛶࢆホ౯ࡍࡿヨ㦂ἲ࡛ࠊࢺࢵࣉࢲ
࢘ࣥ᪉ᘧ࡛ࡢࡳ⏝࠸ࡽࢀࡿࠋ
in vitro ▷᫬㛫᭚㟢ἲ㸦Short Time Exposure In Vitro Test Methodࠊ௨ୗ STE ἲ㸧ࡣࠊゅ⭷ୖ⓶ࡢᦆയࡢస⏝ᶵᗎ࡛࠶ࡿゅ⭷ୖ⓶⣽⬊࡟ᑐࡍࡿ⣽⬊ẘᛶࢆᣦᶆ࡟⏝࠸࡚ࠊ║่⃭ᛶࢆホ౯ࡍࡿヨ㦂ἲ࡛࠶ࡿࠋࡍ࡞ࢃࡕ STE ἲ࡛ࡣࠊ࢘ࢧࢠゅ⭷⏤᮶ᰴ໬⣽⬊࡛࠶ࡿ SIRC⣽⬊࡟⿕㦂≀㉁ࡢᕼ㔘ᾮࢆ 5 ศ㛫᭚㟢ࡋࡓᚋࠊMTT ࡢྲྀࡾ㎸ࡳ㔞ࢆᇶ࡟⣽⬊⏕Ꮡ⋡ࢆᐃࡋ㸦MTT 㑏ඖἲ㸧ࠊ⿕㦂≀㉁㸦ᮍᕼ㔘㸧ࡢ║่⃭ᛶࢆホ౯ࡋ࡚࠸ࡿ㸦Takahashi et al. 2008㸧ࠋ
STE ἲࡣ᪥ᮏື≀ᐇ㦂௦᭰ἲᏛ఍㸦Sakaguchi et al. 2011㸧࡜ JaCVAM㸦Kojima et al. 2013㸧ࡢࣂࣜࢹ࣮ࢩࣙࣥࢆ⤒࡚ࠊࢺࢵࣉࢲ࢘ࣥ᪉ᘧ࡟࠾࠸࡚ UN GHS ༊ศ 1 ≀㉁ࢆ᳨ฟࡍࡿ᪉
ἲ࠾ࡼࡧ࣎ࢺ ࣒࢔ࢵ ࣉ᪉ᘧ ࡟࠾࠸ ࡚ UN GHS ༊ศእ≀ ㉁ࢆ ᳨ฟࡍࡿ᪉ἲ ࡜ࡋ࡚
ICCVAM/NICEATM ࡟ࡼࡾ➨୕⪅ホ౯ࢆཷࡅࠊࡑࡢሗ࿌᭩㸦Summary Review Document:SRD㸧ࡀ 2013 ᖺ 6 ᭶࡟බ⾲ࡉࢀࡓࠋࡑࡢᚋࠊ2015 ᖺ 7 ᭶࡟ OECD ࡟ࡼࡾࢺࢵࣉࢲ࣭࢘ࣥ࣎ࢺ࣒࢔ࢵࣉ୧᪉ᘧࡢ║่⃭ᛶヨ㦂௦᭰ἲ࡜ࡋ࡚ࢸࢫࢺ࢞࢖ࢻࣛ࢖ࣥ࡟᥇ᢥࡉࢀࡓ㸦TG 491㸧ࠋᮏሗ࿌᭩ࡣ ICCVAM/NICEATM ࡢ SRD ࡸⓎ⾲ㄽᩥ࡞࡝ࢆࡶ࡜࡟ OECD TG 491 ࡟᥇ᢥ
ࡉࢀࡓ STE ἲࡢᴫせࢆㄝ᫂ࡋࠊᮏጤဨ఍ࡢពぢ࠾ࡼࡧホ౯ࢆ㏙࡭ࡓࡶࡢ࡛࠶ࡿࠋ2㸬ヨ㦂ἲࡢ఩⨨࡙ࡅ
STE ἲࡣࠊUN GHS ༊ศ 1 ≀㉁࡛࠶ࡿ༢୍≀㉁࠾ࡼࡧΰྜ≀ࢆࢺࢵࣉࢲ࢘ࣥ᪉ᘧ᳨࡛
ฟࡍࡿ㝿࡟᭱ึ࡟⏝࠸ࡿヨ㦂ἲ࡛࠶ࡿࠋࡲࡓࠊSTE ἲࡣࠊUN GHS ༊ศእ≀㉁࡛࠶ࡿ༢
୍≀㉁࠾ࡼࡧΰྜ≀ࢆ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ᳨࡛ฟࡍࡿ㝿࡟᭱ึ࡟⏝࠸ࡿヨ㦂ἲ࡛ࡶ࠶ࡿࠋ
3㸬ヨ㦂ἲࡢཎ⌮║࡟␗≀ࡀධࡗࡓሙྜࠊ║ࡢ่⃭ᛶࡣ᭱⾲㠃ࡢ⣽⬊യᐖ࠿ࡽጞࡲࡿࠋSTE ἲࡣࡇࢀ࡟

511ὀ┠ࡋ࡚ࠊゅ⭷ୖ⓶⣽⬊࡟ᑐࡍࡿ⣽⬊ẘᛶࢆᣦᶆ࡜ࡋ࡚║่⃭ᛶࢆホ౯ࡍࡿヨ㦂ἲ࡛࠶ࡿࠋࢥࣥࣇ࢚ࣝࣥࢺ࡟༢ᒙᇵ㣴ࡋࡓ SIRC ⣽⬊࡟⿕㦂≀㉁ᕼ㔘ᾮࢆ 5 ศ㛫᭚㟢ࡋࡓᚋࠊ
MTT ࡢྲྀࡾ㎸ࡳ㔞࡛ ᐃࡋࡓ⣽⬊⏕Ꮡ⋡ࢆ࢚ࣥࢻ࣏࢖ࣥࢺ࡟⏝࠸ࡿࠋࡇࢀࡣࠊMTT ࡀ⬺Ỉ⣲㓝⣲ࡢᇶ㉁࡜࡞ࡿᛶ㉁ࢆ฼⏝ࡋࠊ⣽⬊ෆ࡟ྲྀࡾ㎸ࡲࢀࡓ MTT ࡀ࣑ࢺࢥࣥࢻࣜ࢔ෆ⬺Ỉ⣲㓝⣲࡟ࡼࡾ㑏ඖࡉࢀࠊ⏕ᡂࡉࢀࡓ࣐࣍ࣝࢨࣥ㔞ࡀ⏕Ꮡ⣽⬊ᩘ࡟ẚ౛ࡍࡿࡇ࡜ࢆ฼
⏝ࡋ࡚࠸ࡿ㸦MTT 㑏ඖἲ㸧ࠋ║࡟⁐ᾮࡀධࡗࡓሙྜࠊࣄࢺ࡛ࡣࡑࡢ኱㒊ศࡀ 1㹼2 ศ࡛║ෆ࠿ࡽ᤼ฟࡉࢀࠊ࢘ࢧࢠ࡛
ࡣ 3㹼4 ศ࡛ 80%ࡀ᤼ฟࡉࢀࡿ࡜ሗ࿌ࡉࢀ࡚࠸ࡿࠋࡇࡢࡼ࠺࡞ᐇ㝿ࡢ᭚㟢≧ἣࢆ⪃៖ࡋ࡚ࠊ
STE ἲࡣ㏻ᖖࡢ⣽⬊ẘᛶヨ㦂࡜ẚ࡭࡚▷᫬㛫᭚㟢ࡢヨ㦂࡜ࡋ࡚タィࡉࢀ࡚࠸ࡿࠋ4㸬ヨ㦂ᡭ㡰 STE ἲࡢᡭ㡰ࡢヲ⣽ࡣ TG 491 ࡟᭩࠿ࢀ࡚࠸ࡿࡀࠊᴫせࡣ௨ୗࡢ㏻ࡾ࡛࠶ࡿࠋ
4-1. ⣽⬊ࡢ‽ഛ
SIRC ⣽⬊ࡣ 10%㸦v/v㸧࢘ࢩ⫾ඣ⾑Ύࠊ2 mM L-ࢢࣝࢱ࣑ࣥࠊ50㹼100 unit/mL ࣌ࢽࢩ
ࣜࣥࠊ50㹼100 μg/mL ࢫࢺࣞࣉࢺ࣐࢖ࢩࣥࢆῧຍࡋࡓ Eagle ᭱ᑠᚲ㡲ᇵᆅ࡟࡚ 37˚Cࠊ5%
CO2 Ꮡᅾୗ࡛ᇵ㣴ࡍࡿࠋࢥࣥࣇ࢚ࣝࣥࢺ࡟࡞ࡿࡲ࡛ᇵ㣴ࡋࡓ⣽⬊ࢆࢺࣜࣉࢩࣥ EDTA ⁐ᾮ࡟ࡼࡾ๤ࡀࡋࠊ⥅௦⏝ᇵ㣴ࣇࣛࢫࢥ࡟᧛✀ࡍࡿࠋヨ㦂࡟ࡣ⥅௦ᩘ 25 ᅇࡲ࡛ࡢ⣽⬊ࢆ౑⏝ࡍࡿࠋヨ㦂࡟⏝࠸ࡿ㝿ࡣࠊヨ㦂ᐇ᪋᫬࡟ࢥࣥࣇ࢚ࣝࣥࢺ㸦>80%㸧࡟࡞ࡿࡼ࠺࡟ࠊ๓ᇵ㣴ᮇ㛫
ࡀ 4 ᪥㛫࡞ࡽࡤ࢙࢘ࣝ࠶ࡓࡾ 6.0 × 103 cellsࠊ5 ᪥㛫࡞ࡽࡤ࢙࢘ࣝ࠶ࡓࡾ 3.0 × 103 cells ࡟ㄪ〇ࡋ 96 ࢙࢘ࣝᖹᯈࣉ࣮ࣞࢺ࡟ 200 μL ࡎࡘ᧛✀ࡍࡿࠋ
4-2. ヨ㦂ࢧࣥࣉࣝࡢㄪ〇⏕⌮㣗ሷỈࠊ5%㸦w/w㸧DMSO㸦CAS# 67-68-5㸧ࢆྵࡴ⏕⌮㣗ሷỈࠊ࣑ࢿࣛࣝ࢜࢖ࣝ

612

㸦CAS# 8042-47-5㸧ࡢ୰࠿ࡽ㐺ษ࡞⁐፹ࢆᅗ 1 ࡟ᚑࡗ࡚㑅ᢥࡍࡿࠋヨ㦂࡟ࡣ⿕㦂≀㉁ࡢ 5% ࠾ࡼࡧ 0.05% ᕼ㔘ᾮ㸦⁐ᾮ࠶ࡿ࠸ࡣᠱ⃮ᾮ㸧ࢆ౪ࡍࡿࠋ㝧ᛶᑐ↷࡟ࡣ SLS ࡢ 0.01% ⏕⌮㣗ሷỈ⁐ᾮࢆ⏝࠸ࡿࠋࡇࢀ࡟ຍ࠼࡚ࠊ⁐፹ᑐ↷ࠊ᧯సᑐ↷㸦ᇵᆅᑐ↷㸧࠾ࡼࡧࣈࣛࣥࢡ㸦⣽⬊࡞ࡋᇵᆅࡢࡳ㸧ࡶタࡅࡿࠋ
4-3. ᭚㟢࣭⣽⬊⏕Ꮡ⋡ࡢ⟬ฟ SIRC ⣽⬊ࢆ๓ᇵ㣴ࡋ࡚ࢥࣥࣇ࢚ࣝࣥࢺ࡜࡞ࡗࡓ 96 ࢙࢘ࣝᖹᯈࣉ࣮ࣞࢺࢆ௨ୗࡢࡼ࠺࡟ฎ⌮ࡍࡿࠋྛ࢙࢘ࣝ࠿ࡽᇵᆅࢆ㝖ཤࡋࠊ⿕㦂≀㉁ᕼ㔘ᾮ㸦5%ࠊ0.05%㸧࠾ࡼࡧᑐ↷≀㉁ࢆࡑࢀࡒࢀ 200 μL ࡎࡘῧຍࡋ 5 ศ㛫ᐊ ࡛᭚㟢ࡍࡿࠋ᭚㟢⤊஢ᚋࠊヨ㦂ࢧࣥࣉࣝࢆ㝖ཤࡋࠊࣜࣥ㓟⦆⾪ᾮ 200 μL ࡛ 2 ᅇὙίࡍࡿࠋMTT ⁐ᾮࢆ 200 μL ῧຍࡋࠊ37˚Cࠊ5% CO2Ꮡᅾୗ࡛ 2 ᫬㛫཯ᛂࡉࡏࡿࠋ཯ᛂᚋ MTT ⁐ᾮࢆ㝖ཤࡋࠊ࣐࣍ࣝࢨࣥᢳฟᾮࢆ 200 μL ῧຍࡋࠊ1 ᫬㛫ᐊ ᬯᡤ࡛࣐࣍ࣝࢨࣥࢆᢳฟࡋࠊࡑࡢ྾ගᗘࢆࣉ࣮ࣞࢺ࣮ࣜࢲ࣮࡟ࡼࡾ 570
nm㸦OD570㸧࡛ ᐃࡍࡿࠋ ヨ㦂ࢧࣥࣉࣝẖ࡟ 3 ࢙࢘ࣝࢆ⏝࠸ࠊ3 ࢙࢘ࣝࡢᖹᆒ OD570 ࢆ⣽⬊⏕Ꮡ⋡⟬ฟ࡟⏝࠸ࡿࠋ⣽⬊⏕Ꮡ⋡ =OD570 ヨ㦂ࢧࣥࣉࣝ㸫OD570 ࣈࣛࣥࢡOD570 ⁐፹ᑐ↷㸫OD570 ࣈࣛࣥࢡ× 100࡞࠾ࠊヨ㦂ࢧࣥࣉࣝฎ⌮⩌ࡢ⣽⬊⏕Ꮡ⋡ࡀ࣐࢖ࢼࢫ࡟࡞ࡗࡓሙྜࡣࠊ⏕Ꮡ⋡ࢆࢮࣟ࡜ࡍ
ࡿࠋ
4-4. ║่⃭ᛶุᐃ ௨ୖࡢᡭ㡰࡛ᐇ㦂ࢆ 3 ᅇᐇ᪋ࡋࠊࡑࢀࡒࢀ࡛ᚓࡽࢀࡓ⣽⬊⏕Ꮡ⋡ࡢᖹᆒࢆ᭱⤊ุᐃ࡟⏝࠸ࡿࠋ║่⃭ᛶ GHS ศ㢮ࡢุᐃࡣ⾲ 1 ࡟♧ࡋࡓ㏻ࡾ࡛࠶ࡿࠋ
⾲ 1. ║่⃭ᛶ GHS ศ㢮ࡢุᐃ⿕㦂≀㉁ᕼ㔘⃰ᗘᖹᆒ⏕Ꮡ⋡

0.05%> 70%5%

> 70%

0.05%

> 70%

5%

< 70%

0.05%

< 70%5%< 70%⿕㦂≀㉁ࡢ GHS ศ㢮༊ศእศ㢮࡛ࡁ࡞࠸
༊ศ 14-5. ⤖ᯝࡢᢎㄆᇶ‽௨ୗࡢ 4 ᮲௳ࢆ‶ࡓࡋࡓሙྜࠊヨ㦂ࡢ⤖ᯝࢆᢎㄆࡍࡿࠋ1) ᧯సᑐ↷ࡢ྾ගᗘࡀࣈࣛࣥࢡῶ⟬ᚋ 0.3 ௨ୖ࡛࠶ࡿࡇ࡜ࠋ2) ᐇ㦂࡟⏝࠸ࡓ⁐፹ᑐ↷ࡍ࡭࡚࡟࠾࠸࡚ࠊ⣽⬊⏕Ꮡ⋡ࡀ᧯సᑐ↷ࡢ 80%௨ୖ࡛࠶ࡿࡇ࡜ࠋ7133) 㝧ᛶᑐ↷ࡢ⣽⬊⏕Ꮡ⋡ࡀጇᙜ࡞⠊ᅖὀ㸧࡟཰ࡲࡿࡇ࡜ࠋ4) 3 ᅇࡢᐇ㦂ࡢ⣽⬊⏕Ꮡ⋡ࡢ SD ࡀ⿕㦂≀㉁ 5%ࠊ0.05% ᕼ㔘ᾮ࡝ࡕࡽ࡛ࡶ 15%ᮍ‶࡛࠶ࡿࡇ࡜ࠋ1)㹼4) ࡢ᮲௳ࡢ࠸ࡎࢀ࠿ࡀ‶ࡓࡉࢀ࡞࠸ሙྜ࡟ࡣࢹ࣮ࢱࢆࡍ࡭࡚◚Რࡋࠊ᪂ࡓ࡟⊂❧ࡋࡓ 3 ᅇࡢᐇ㦂ࢆᐇ᪋ࡍࡿࠋ
5㸬ヨ㦂ἲࡢṇ☜ᛶ௨ୗࡢࣂࣜࢹ࣮ࢩࣙࣥヨ㦂➼ࡢ⤖ᯝࡀ STE ἲࡢṇ☜ᛶࡢ᳨ウ࡟⏝࠸ࡽࢀࡓࠋ
࣭ Takahashi et al.㸦2009㸧– ࣉࣞࣂࣜࢹ࣮ࢩࣙࣥヨ㦂 I 44 ≀㉁࣭ Takahashi et al.㸦2010㸧– ࣉࣞࣂࣜࢹ࣮ࢩࣙࣥヨ㦂 II 70 ≀㉁࣭ Sakaguchi et al.㸦2011㸧– ࣂࣜࢹ࣮ࢩࣙࣥヨ㦂 I 25 ≀㉁࣭ Kojima et al.㸦2013㸧– ࣂࣜࢹ࣮ࢩࣙࣥヨ㦂 II 40 ≀㉁࣭ ⰼ⋤♫ෆࢹ࣮ࢱ – Takahashi et al.㸦2011㸧࠾ࡼࡧᮍⓎ⾲♫ෆࢹ࣮ࢱ 23 ≀㉁࣭ ⰼ⋤♫ෆࢹ࣮ࢱ㸦㏣ຍศ㸧– ⏺㠃άᛶ๣࠾ࡼࡧ⏺㠃άᛶ๣ྵ᭷ࡢฎ᪉ 52 ≀㉁࣭ Saito et al.㸦2015㸧– ΰྜ≀ 40 ≀㉁
Saito et al.ࡢࢹ࣮ࢱࢆ㝖ࡃ 169 ≀㉁ࡢࢹ࣮ࢱࢆ⏝࠸࡚ ICCVAM/NICEATM ࡟ࡼࡿṇ☜ᛶࡢ᳨ウࡀ⾜ࢃࢀࡓࠋࡑࡢ࠺ࡕࠊGHS ࡢ║่⃭ᛶศ㢮ࢆ⾜࠺ࡢ࡟㐺ษ࡞ື≀ヨ㦂ࡢࢹ࣮ࢱࡀ࡞࠸≀㉁ࡣṇ☜ᛶࡢ᳨ウᑐ㇟࠿ࡽ㝖࠿ࢀࡓࠋ1 ࡘࡢ≀㉁࡟ᑐࡋ࡚」ᩘࡢヨ㦂᪋タ࡛ࡢ
STE ἲࡢุᐃࡀ࠶ࡿሙྜࡣࠊヨ㦂᪋タᩘࡀ᭱ࡶከ࠸ุᐃࢆ᥇⏝ࡋࡓࠋࡑࡢヨ㦂᪋タᩘࡀྠᩘ࡟࡞ࡗࡓሙྜࡣࠊ่⃭ᛶࡢ㧗࠸ุᐃࡢ᪉ࢆ᥇⏝ࡋࡓࠋ࡞࠾ࠊICCVAM/NICEATM ࡢ᳨ウ࡛ࡣ MTT ࢆ┤᥋㑏ඖࡍࡿ≀㉁㸦࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡛ࡣ༊ศእ࡜ุᐃࡉࢀࡓ≀㉁ࡢࡳ㸧ࡣ᳨ウᑐ㇟࠿ࡽእࡉࢀ࡚࠸ࡓࡀࠊ2 ḟඖ⣽⬊ᇵ㣴⣔ࢆ⏝࠸ࡿ STE ἲ࡟࠾࠸࡚ࡣὙί࡟ࡼࡾ⿕㦂≀㉁ࡣ༑ศྲྀࡾ㝖࠿ࢀࡿࡢ࡛ࠊ௨ୗࡢṇ☜ᛶࡢ᳨ウ࡛ࡣ᥇⏝ࡋࡓࠋ
Saito et al. ࡢࢹ࣮ࢱࡣ 5%ᕼ㔘ࡢ⤖ᯝࡢࡳࢆྵࡳࠊ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡛ࡢΰྜ≀ࡢホ౯࡟࠾ࡅࡿṇ☜ᛶࢆ᳨ウࡋ࡚࠸ࡿࠋ
5-1. ࢺࢵࣉࢲ࢘ࣥ᪉ᘧ㸫GHS ༊ศ 1 ࡢ≀㉁ࡢ᳨ฟ
ࢺࢵࣉࢲ࢘ࣥ᪉ᘧࡢṇ☜ᛶࡢ᳨ウ࡟ࡣ 125 ≀㉁ࡢࢹ࣮ࢱࡀ⏝࠸ࡽࢀࡓ㸦Appendix 1㸧ࠋࡑࡢ⤖ᯝࡣࠊṇ☜ᗘ 83.2%㸦104/125㸧ࠊഇ㝧ᛶ⋡ 1.2%㸦1/86㸧ࠊഇ㝜ᛶ⋡ 51.3%㸦20/39㸧࡛࠶ࡗࡓࠋഇ㝜ᛶࢆ♧ࡋࡓ 20 ≀㉁ࡢ࠺ࡕࠊ࢔ࣝࢥ࣮ࣝ㢮ࡀ 8 ≀㉁ࠊ࢝ࣝ࣎ࣥ㓟㢮ࡀ 5 ≀㉁ࠊࡲࡓሷ㢮ࡀ 3 ≀㉁࠶ࡗࡓࠋࡑࡢ࡯࠿ࠊ࢚ࢫࢸࣝ㢮ࡸ࣊ࢸࣟࢧ࢖ࢡࣜࢵࢡ໬ྜ≀࡞࡝࡛ഇ㝜ᛶࢆ♧ࡋࡓ≀㉁ࡀ࠶ࡗࡓࠋഇ㝧ᛶ࡜࡞ࡗࡓ 1 ≀㉁ࡣ㠀࢖࢜ࣥᛶ⏺㠃άᛶ๣࡛࠶ࡗࡓࠋ࢔ࣝࢥ࣮ࣝ㢮ࡸ࢚ࢫࢸࣝ㢮࡞࡝ື≀ヨ㦂࡛ᚓࡽࢀࡿ║่⃭ᛶศ㢮࡜୍⮴ࡋ࡞࠸≀㉁ࡢ๭ྜࡀ㧗࠿ࡗࡓ໬Ꮫ≀㉁⩌ࢆ㝖࠸࡚ࡶࠊṇ☜ᛶࡢᩘ್࡟㢧ⴭ࡞ᨵၿࡣぢࡽࢀ࡞࠿ࡗࡓࠋ

ὀ㸧ᐇ᪋᪋タࡢ㐣ཤࡢࢹ࣮ࢱ࠿ࡽồࡵࡽࢀࡿᖹᆒ⣽⬊⏕Ꮡ⋡s2SD ࡟཰ࡲࡿࡇ࡜ࠋୖ㝈࣭ୗ㝈್ࡣ 3 ࣨ᭶ࡈ࡜࡟᭦᪂ࡍ
࡭ࡁ࡛࠶ࡿࠋᐇ᪋ᐇ⦼ࡀ 1 ࣨ᭶࡟ 1 ᅇᮍ‶ࡢ᪋タ࡟࠾࠸࡚ࡣୖ㝈࣭ୗ㝈್ࡢ᭦᪂ࡣヨ㦂ᐇ᪋ࡈ࡜࡟⾜࠺ࡇ࡜ࠋ㐣ཤࡢࢹ࣮ࢱࡀ୙༑ศ࡞᪋タ࡟࠾࠸࡚ࡣࠊSTE ἲ㛤Ⓨ᪋タࡀタᐃࡋࡓୖ㝈࣭ୗ㝈್㸦21.1%㹼62.3%㸧ࢆ⏝࠸࡚ᵓࢃ࡞࠸ࠋ

814

ࡍ࡛࡟ࢺࢵࣉࢲ࢘ࣥ᪉ᘧ࡛ࡢࣂࣜࢹ࣮ࢩࣙࣥࡀ⤊஢ࡋ࡚࠸ࡿ௚ࡢ௦᭰ἲ࡜ STE ἲࡢṇ☜ᛶࡢẚ㍑ࢆ⾲ 2 ࡟ࡲ࡜ࡵࡓࠋ
5-2. ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ㸫GHS ༊ศእࡢ≀㉁ࡢ᳨ฟ
࣎ࢺ࣒࢔ࢵࣉ᪉ᘧࡢṇ☜ᛶࡢ᳨ウ࡟ࡣ 130 ≀㉁ࡢࢹ࣮ࢱࡀ⏝࠸ࡽࢀࡓ㸦Appendix 1㸧ࠋࡑࡢ⤖ᯝࡣࠊṇ☜ᗘ 84.6%㸦110/130㸧ࠊഇ㝧ᛶ⋡ 19.3%㸦11/57㸧ࠊഇ㝜ᛶ⋡ 12.3%㸦9/73㸧
࡛࠶ࡗࡓࠋ㧗࠸ഇ㝜ᛶ⋡ࢆ♧ࡋࡓ≀㉁ࡣࠊሷ㢮ࠊⅣ໬Ỉ⣲ࠊ࢔ࣝࢥ࣮ࣝ㢮࡞࡝ࡀ࠶ࡗࡓࠋ
ࡲࡓࠊᅛయ㸦13.5%㸧ࡢ᪉ࡀᾮయ㸦4.3%㸧ࡼࡾࡶഇ㝜ᛶ⋡ࡀ㧗࠿ࡗࡓࠋࡇࢀࡽࡢ໬Ꮫ≀㉁⩌ࡢࢹ࣮ࢱࢆࡑࢀࡒࢀ㝖࠸࡚ࡶࠊṇ☜ᛶࡢᩘ್࡟㢧ⴭ࡞ᨵၿࡣぢࡽࢀ࡞࠿ࡗࡓࠋ㐺⏝⠊ᅖ࡜ࡋ࡚ࠊ⵨Ẽᅽࡀ㧗࠸≀㉁㸦> 6 kPa㸧࡜⏺㠃άᛶ๣࡛ࡣ࡞࠸ᅛయࢆ㝖࠸ࡓሙྜࡣࠊṇ☜ᗘ 90.2%㸦92/102㸧ࠊഇ㝧ᛶ⋡ 18.8%㸦9/48㸧ࠊഇ㝜ᛶ⋡ 1.9%㸦1/54㸧࡛࠶ࡗࡓࠋഇ㝜ᛶࢆ♧ࡋࡓ≀㉁ࡣື≀ヨ㦂࡛ࡢ GHS ศ㢮ࡀ༊ศ 2B ࡛࠶ࡿ Toluene ࡛࠶ࡗࡓࠋࡍ࡛࡟࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡛ࡢࣂࣜࢹ࣮ࢩࣙࣥࡀ⤊஢ࡋ࡚࠸ࡿ௚ࡢ௦᭰ἲ࡜ STE ἲࡢṇ☜ᛶࡢẚ㍑ࢆ
⾲ 3 ࡟ࡲ࡜ࡵࡓࠋ
⾲ 2. ࢺࢵࣉࢲ࢘ࣥ᪉ᘧ࡛ࡢ STE ἲ࡜ࣂࣜࢹ࣮ࢩࣙࣥࡀ⤊஢ࡋ࡚࠸ࡿ௦᭰ἲ࡜ࡢṇ☜ᛶࡢẚ㍑
ヨ㦂ἲ≀㉁ᩘ

STE
BCOP
ICE
CM
FL

125
188
144
82151

ṇ☜ᗘ
%
No.
83.2
104/125
79.3
149/188
83.3
120/144
90.2
74/82
77.5
117/151

ഇ㝧ᛶ⋡
%
No.
1.2
1/86
23.6
29/123
7.9
9/114
2.1
1/48
6.8
7/103

ഇ㝜ᛶ⋡
%
No.
51.3
20/39
15.4
10/65
50.0
15/30
20.6
7/34
56.3
27/48

⾲ 3. ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡛ࡢ STE ἲ࡜ࣂࣜࢹ࣮ࢩࣙࣥࡀ⤊஢ࡋ࡚࠸ࡿ௦᭰ἲ࡜ࡢṇ☜ᛶࡢẚ㍑

13018815253

ṇ☜ᗘ
%
No.
84.6
110/13066.5
125/18882.2
125/152
67.9
36/53

ഇ㝧ᛶ⋡
%
No.
19.3
11/57
69.2
63/91
32.9
26/79
68.0
17/25

ഇ㝜ᛶ⋡
%
No.
12.3
9/73
0.0
0/97
1.4
1/73
0.0
0/28

102

90.2

18.8

1.9ヨ㦂ἲ≀㉁ᩘ

STE
BCOPICECM
STE*

92/102

9/48

1/54* ⵨Ẽᅽ > 6 kPa ࡢ≀㉁ࠊ࠾ࡼࡧࠊ⏺㠃άᛶ๣௨እࡢᅛయࢆ㝖࠸ࡓሙྜ5-3. ΰྜ≀
๓㏙ࡢ ICCVAM/NICEATM ࡟ࡼࡿṇ☜ᛶࡢ᳨ウ࡟ࡣΰྜ≀ࡀ 10 ≀㉁ྵࡲࢀ࡚࠸ࡿࠋࡑ
ࡢ࠺ࡕࠊ༊ศ 1 ࡢ 1 ≀㉁ࡣศ㢮୙ྍ࡜ุᐃࡉࢀࡓࠋ༊ศእࡢ 4 ≀㉁୰ 3 ≀㉁ࡣ༊ศእ࡜
ุᐃࡉࢀࡓࠋ

915

ICCVAM/NICEATM ࡟ࡼࡿṇ☜ᛶࡢ᳨ウ࡜ࡣู࡟ࠊSaito et al. ࡢ 40 ΰྜ≀ࢆ⏝࠸ࡓ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡟࠾ࡅࡿṇ☜ᛶࡢ᳨ウ࡟ࡼࡿ࡜ࠊṇ☜ᗘ 87.5% 㸦35/40㸧ࠊഇ㝧ᛶ⋡ 50.0%
㸦5/10㸧
ࠊഇ㝜ᛶ⋡ 0.0%㸦0/30㸧࡛࠶ࡗࡓࠋ
6㸬ヨ㦂ἲࡢಙ㢗ᛶ௨ୗࡢࣂࣜࢹ࣮ࢩࣙࣥヨ㦂ࡢ⤖ᯝࡀ STE ἲࡢಙ㢗ᛶࡢ᳨ウ࡟⏝࠸ࡽࢀࡓࠋ
࣭ Takahashi et al.㸦2009㸧– ࣉࣞࣂࣜࢹ࣮ࢩࣙࣥヨ㦂 I
࣭ Takahashi et al.㸦2010㸧– ࣉࣞࣂࣜࢹ࣮ࢩࣙࣥヨ㦂 II
࣭ Sakaguchi et al.㸦2011㸧– ࣂࣜࢹ࣮ࢩࣙࣥヨ㦂 I
࣭ Kojima et al.㸦2013㸧– ࣂࣜࢹ࣮ࢩࣙࣥヨ㦂 II6-1. ᢏ⾡⛣㌿ᛶ
STE ἲࢆᐇ᪋ࡍࡿࡓࡵ࡟ᚲせ࡞⿦⨨࣭ჾලࡣࠊ୍⯡ⓗ࡞↓⳦໬ࡢ⣽⬊ᇵ㣴࡟⏝࠸ࡿࡶࡢ࡛ࠊධᡭࡣᐜ࡛᫆࠶ࡿࠋᡭᢏࡶᢏ⾡ⓗ࡟」㞧࡞ࡶࡢ࡛ࡣ࡞࠸ࠋ2 ࡘࡢࣉࣞࣂࣜࢹ࣮ࢩ
ࣙࣥヨ㦂࡟࠾࠸࡚ࡶᢏ⾡⛣㌿ᛶ࡟ࡘ࠸࡚ࡢၥ㢟ࡣᣦ᦬ࡉࢀ࡚࠸࡞࠸ࠋ6-2. ᪋タෆ෌⌧ᛶSTE ἲࡣ 1 ࡘࡢヨ㦂࡛ 3 ࡘࡢ⊂❧ࡋࡓᐇ㦂ࢆ⾜࠺ࡓࡵࠊಶࠎࡢᐇ㦂࠿ࡽᚓࡽࢀࡓ⣽⬊⏕Ꮡ⋡ࡀ᪋タෆ෌⌧ᛶࡢ᳨ウ࡟⏝࠸ࡽࢀࡓࠋ༊ศእ࡜ุᐃࡉࢀࡓ≀㉁ࡢ 5%ᕼ㔘ᾮ࡛ࡢ⣽⬊⏕Ꮡ⋡ࡢኚືಀᩘࡣ 0.3㹼23.5%࡛࠶ࡗࡓࠋ༊ศእ࡜ุᐃࡉࢀ࡞࠿ࡗࡓ≀㉁࡛ࡣ⏕Ꮡ⋡ࡀᴟࡵ࡚ప࠸್࡟࡞ࡿࡓࡵࠊࡑࡢኚືಀᩘࡣ㧗࠸್ࢆ♧ࡋࡓࠋ㝧ᛶᑐ↷࡜ࡋ࡚⏝࠸ࡽࢀࡿ 0.01% SLS ࡢᖹᆒ⣽⬊⏕Ꮡ⋡ࡣ 41.7%㸦n = 71㸧࡛࠶ࡾࠊኚືಀᩘࡣ 24.7%࡛࠶ࡗࡓࠋ
6-3. ᪋タ㛫෌⌧ᛶ5 ᪋タ࡛⾜ࢃࢀࡓ Sakaguchi et al.ࡢࣂࣜࢹ࣮ࢩࣙࣥヨ㦂 I ࡟࠾࠸࡚ࠊࡑࢀࡒࢀࡢ᪋タ࡛ᚓࡽࢀࡓᕼ㔘⃰ᗘࡈ࡜ࡢ 25 ≀㉁ࡢᖹᆒ⣽⬊⏕Ꮡ⋡ࡢ SD ࡣ 0.3㹼20.1%࡛࠶ࡗࡓࠋSD ࡣᇶᮏⓗ࡟ᑠࡉࡃࠊⰋዲ࡞᪋タ㛫෌⌧ᛶࡀ☜ㄆࡉࢀࡓࠋ25 ≀㉁ࡢ GHS ศ㢮ࡢุᐃ࡟ࡘ࠸
࡚ 5 ᪋タࡍ࡭ุ࡚࡛ᐃࡀ୍⮴ࡋࡓࡢࡣ 21 ≀㉁ࠊ1 ᪋タุ࡛ᐃࡀ␗࡞ࡗࡓࡢࡣ 3 ≀㉁࡛ࠊ2 ᪋タุ࡛ᐃࡀ␗࡞ࡗࡓࡢࡣ 1 ≀㉁࡛࠶ࡗࡓࠋ
 STE ἲࢆᐇ᪋ࡍࡿヨ㦂᪋タ࡬㐺ษ࡞ᢏ⾡⛣㌿ࡀ㐩ᡂ࡛ࡁࡓࡇ࡜ࢆ☜࠿ࡵࡿ࡟ࡣࠊ
Appendix 2 ࡢ⇍㐩ᗘ☜ㄆ≀㉁ࢆ⏝࠸ࡿࠋ
7㸬ヨ㦂ἲࡢ㐺⏝⠊ᅖ
STE ἲࡢ㐺⏝࡟ࡣヨ㦂ἲࡢᛶ㉁ୖࠊࡲࡓࠊṇ☜ᛶࡢほⅬ࠿ࡽ௨ୗࡢไ㝈ࡀタࡅࡽࢀࡿࠋ1) ⏕⌮㣗ሷỈࠊ5%㸦w/w㸧DMSO ࢆྵࡴ⏕⌮㣗ሷỈࠊ࠾ࡼࡧ࣑ࢿࣛࣝ࢜࢖ࣝࡢ࠸ࡎࢀ࡟ࡶ⁐ゎࡋ࡞࠸ࠊ࠶ࡿ࠸ࡣࡑࢀࡽ⁐፹୰࡛ᆒ୍ศᩓࡋ࡚࠸ࡿ≧ែࡀ 5 ศ௨ୖಖࡓࢀ࡞࠸≀㉁ࡣ㐺⏝୙ྍ⬟࡛࠶ࡿࠋ2) ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧࢆ༢୍≀㉁࡟㐺⏝ࡍࡿሙྜࠊ⵨Ẽᅽࡀ 6 kPa ࢆ㉸࠼ࡿ≀㉁࠾ࡼࡧ
⏺㠃άᛶ๣࡛ࡣ࡞࠸ᅛయࡣࠊࡇࢀࡽ≀㉁⩌ࡀ㧗࠸ഇ㝜ᛶ⋡ࢆ♧ࡍࡇ࡜࠿ࡽࠊ㐺⏝࠿

1016ࡽ㝖እࡉࢀࡿࠋᅛయΰྜ≀࡟㐺⏝ࡍࡿሙྜࡣࠊ⏺㠃άᛶ๣ࡢࡳ࠿ࡽᵓᡂࡉࢀࡿ≀㉁ࡣᑐ㇟࡟ࡍࡿࡀࠊࡑࢀ௨እࡢ≀㉁ࡣ㝖እࡍࡿࠋࡲࡓࠊ⵨Ẽᅽࡢ㧗࠸㸦> 6 kPa㸧≀㉁ࢆྵࡴΰྜ≀࡟㐺⏝ࡍࡿሙྜࡣ║่⃭ᛶࡀ㐣ᑠホ౯ࡉࢀࡿྍ⬟ᛶࡀ࠶ࡿࡢ࡛ࠊSTEἲࢆ⏝࠸ࡿṇᙜᛶࢆಶู࡟᳨ウࡍ࡭ࡁ࡛࠶ࡿࠋ3) ࢺࢵࣉࢲ࢘ࣥ᪉ᘧ࡛ࡣࠊ༢୍≀㉁ࢆ⏝࠸ࡿሙྜࡣไ㝈ࡀ࡞ࡃࠊࡲࡓࠊΰྜ≀࡟ࡘ࠸࡚ࡶࣂࣜࢹ࣮ࢩࣙࣥࢹ࣮ࢱࡣ㝈ࡽࢀ࡚ࡣ࠸ࡿࡶࡢࡢࠊ㐺⏝࠿ࡽ㝖እࡍࡿᚲせࡣ࡞࠸ࠋ
8. ᮏጤဨ఍ࡢ⤖ㄽ
STE ἲࡣࠊࡍ࡛࡟ࣂࣜࢹ࣮ࢩࣙࣥࡀ⤊஢ࡋ࡚࠸ࡿ௚ࡢ௦᭰ἲ࡜ẚ㍑ࡋࡓሙྜࠊṇ☜ᛶࠊ෌⌧ᛶࡣྠ⛬ᗘ࡛࠶ࡗࡓࠋ
▷᫬㛫࡛Ᏻ౯࡟ᐇ᪋࡛ࡁࠊ౑⏝⣽⬊ࡢ౪⤥※࡟ไ㝈ࡀ࡞ࡃࠊ≉Ṧ࡞ᶵᮦࡸヨ⸆ࢆᚲせ࡜ࡏࡎࠊᚲせ࡞ᡭᢏࡶ」㞧࡞ࡶࡢ࡛࡞࠸࠿ࡽࠊᢏ⾡⛣㌿ᛶࡣ㧗࠸࡜ุ᩿࡛ࡁࡿࠋ࢞࢖ࢻࣛ࢖ࣥ࡟♧ࡉࢀࡓ⇍㐩ᗘ☜ㄆ≀㉁ࢆ⏝࠸࡚ࠊᐇ᪋ࡍࡿヨ㦂᪋タ࡬㐺ษ࡞ᢏ⾡⛣㌿ࡀ㐩ᡂ࡛ࡁࡓࡇ࡜ࢆ☜࠿ࡵࡿᚲせࡀ࠶ࡿࠋ౑⏝⁐፹࡟୙⁐࡞≀㉁ࠊ࠶ࡿ࠸ࡣᆒ୍࡟ศᩓࡋ࡞࠸≀㉁ࡣヨ㦂࡟㐺ࡉ࡞࠸ࠋ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡛ࡣࠊ⏺㠃άᛶ๣௨እࡢᅛయࡸ⵨Ẽᅽࡢ㧗࠸㸦> 6 kPa㸧≀㉁ࢆ㝖እࡍࡿࡇ࡜࡟
࡞ࡗ࡚࠸ࡿࡀࠊࡑࡢጇᙜᛶࡢ☜ㄆࡣ༑ศ࡛࡞࠸ࠋ
TG 491 ࡟‽ᣐࡋ࡚ᐇ᪋ࡋࡓሙྜࠊࢺࢵࣉࢲ࢘ࣥ᪉ᘧ࡛ UN GHS ༊ศ 1 ≀㉁ࢆ᳨ฟࡍࡿ
᪉ἲࠊ࠾ࡼࡧ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡛ UN GHS ༊ศእ≀㉁ࢆ᳨ฟࡍࡿ᪉ἲ࡜ࡋ࡚⏝࠸ࡿࡇ࡜ࡀ࡛ࡁࡿ࡜ᮏጤဨ఍ࡣ⪃࠼ࡿࠋ

1117

9. ᩥ⊩ICCVAM (2013) Short Time Exposure (STE) Test Method Summary Review Document.
Kojima et al. (2013) Second-phase validation study of the short time exposure test for assessmentof eye irritation potency of chemicals. Toxicol In Vitro 27(6): 1855-1869.
OECD (2012) Test Guideline 437. Bovine Corneal Opacity and Permeability Test Method for
Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring
Classification for Eye Irritation or Serious Eye Damage.
OECD (2012) Test Guideline 438. Isolated Chicken Eye Test Method for Identifying i)
Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye
Irritation or Serious Eye Damage.
OECD (2012) Test Guideline 460. Fluorescein Leakage Test Method for Identifying OcularCorrosives and Severe Irritants.
OECD (2015) Test Guideline 491. Short Time Exposure In Vitro Test Method for Identifying 1)
Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye
Irritation or Serious Eye Damage.
Saito et al. (2015) Predictive performance of the Short Time Exposure test for identifying eye
irritation potential of chemical mixtures. Toxicol In Vitro 29(3): 617-620.
Sakaguchi et al. (2011) Validation study of the Short Time Exposure (STE) test to assess the eyeirritation potential of chemicals. Toxicol In Vitro 25(4): 796-809.
Takahashi et al. (2010) An interlaboratory study of the short time exposure (STE) test using SIRC
cells for predicting eye irritation potential. Cutan Ocul Toxicol 29(2): 77-90.
Takahashi et al. (2009) Inter-laboratory study of short time exposure (STE) test for predicting eyeirritation potential of chemicals and correspondence to globally harmonized system (GHS)
classification. J Toxicol Sci 34(6): 611-626.
Takahashi et al. (2008) Development of the short time exposure (STE) test: an in vitro eye
irritation test using SIRC cells. Toxicol In Vitro 22(3): 760-770.

1218

Appendix 1ST(ἲࡢホ౯࡟⏝࠸ࡽࢀࡓ≀㉁㸦ࡑࡢ㸯㸧ࢺࢵࣉࢲ࢘ࣥ᪉ᘧ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ㐺⏝ไ㝈≀㉁ࢆ㝖እ

125

130

102

࢔ࣝࢥ࣮ࣝ㢮

39

40

36࢔ࣝࢹࣄࢻ㢮

2

20

࢔ࣝ࢝ࣜ

1

10

࢔࣑ࣥ㢮

9

10

8

࣍࢘⣲໬ྜ≀

442࢝ࣝ࣎ࣥ㓟㢮

23

24

19

ሷ⣲໬ྜ≀

1

10

࢚ࢫࢸࣝ㢮

17

18

17

࢚࣮ࢸࣝ㢮

16

16

16〇๣㸦ΰྜ≀㸧

101010ࢢࣜࢥ࣮ࣝ㢮

111࣊ࢸࣟࢧ࢖ࢡࣜࢵࢡ໬ྜ≀9107Ⅳ໬Ỉ⣲

23

24

18

↓ᶵ໬ྜ≀110

ࢣࢺࣥ㢮

8

8

5

ࣛࢡࢺࣥ

1

1

1

Ἔ㢮

5

7

6

ࢽࢺࣜࣝ໬ྜ≀

1

1

1

❅⣲໬ྜ≀

1

1

1

࢜ࢽ࣒࢘໬ྜ≀

11

12

11

ࣇ࢙ࣀ࣮ࣝ㢮

110ከ⎔ᘧ໬ྜ≀

1

1

1

ሷ㢮

17

18

14

◲㯤໬ྜ≀

15

16

12

඲య໬Ꮫ≀㉁༊ศ

ὀ㸧≀㉁࡟ࡼࡗ࡚ࡣ」ᩘࡢ໬Ꮫ≀㉁༊ศ࡟ࡲࡓࡀࡗ࡚࠸ࡿሙྜࡶ࠶ࡿࡓࡵࠊྜィࡣ≀㉁⥲ᩘ࡜ࡣ୍⮴ࡋ࡞࠸ࠋ

13

19

Appendix 1
ST(ἲࡢホ౯࡟⏝࠸ࡽࢀࡓ≀㉁㸦ࡑࡢ㸰㸧ࢺࢵࣉࢲ࢘ࣥ᪉ᘧ

࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ㐺⏝ไ㝈≀㉁ࢆ㝖እ

125

130

102

92

93

79

⵨Ẽᅽ >6kPa-

140

⵨Ẽᅽ <6kPa-

61

61

⵨Ẽᅽ ୙᫂-

18

18

33

37

23

⏺㠃άᛶ๣

-

23

23

㠀⏺㠃άᛶ๣

-140

⵨Ẽᅽ >6kPa-00

⵨Ẽᅽ <6kPa

-

23

10

⵨Ẽᅽ ୙᫂-

14

13

⏺㠃άᛶ๣

45

49

49

⁐๣

34

35

26

໬Ꮫ୰㛫⏘≀

242420

་⸆ရ

20

2013

㤶ᩱ

202013ẅ⹸๣࣭ᢠ⳦๣࣭㜵⭉๣

10107

ሬᩱ

11107඲య≀㉁ࡢ≉ᛶᾮయᅛయ〇ရ༊ศὀ㸧〇ရ༊ศࡣ≀㉁ᩘࡢከ࠸ࡶࡢࢆᢳฟࡋࡓࠋ≀㉁࡟ࡼࡗ࡚ࡣ」ᩘࡢ〇ရ༊ศ࡟ࡲࡓࡀࡗ࡚࠸ࡿሙྜࡶ࠶ࡿࠋ

1420

Appendix 2STE ἲࡢ⇍㐩ᗘ☜ㄆ≀㉁≀㉁ྡ
Benzalkonium chloride(10% aqueous)
Triton X-100 (100%)

STE ἲ࡛ࡢSTE ἲ౑⏝⁐፹ุᐃ༊ศ 1⏕⌮㣗ሷỈ༊ศ㸯ᾮయ༊ศ 1⏕⌮㣗ሷỈ

༊ศ 1

ᅛయ

༊ศ 1

⏕⌮㣗ሷỈ

༊ศ 1

ᅛయ

༊ศ 1

⏕⌮㣗ሷỈ

༊ศ 1

ᾮయ

༊ศ 2A

⏕⌮㣗ሷỈ

ศ㢮୙ྍ

ᾮయ

༊ศ 2A/B㺮㺦㺵㺷㺓㺐㺷ศ㢮୙ྍᾮయ

༊ศ 2A/B⏕⌮㣗ሷỈ

ศ㢮୙ྍ

ᾮయ༊ศእ

⏕⌮㣗ሷỈ

༊ศእ

CAS ␒ྕ໬Ꮫศ㢮

8001-54-5

࢜ࢽ࣒࢘໬ྜ≀ᾮయ

9002-93-1࢚࣮ࢸࣝ㢮ᛶ≧

GHS ศ㢮

㺫㺡㺹㺙㺐㺖㺶㺍㺖໬ྜ≀㸹Acid Red 92

18472-87-2⮯໬໬ྜ≀㸹
ሷ⣲໬ྜ≀࢔ࣝ࢝ࣜ㸹

Sodium hydroxide

1310-73-2

Butyrolactone

96-48-0

1-Octanol

111-87-5

Cyclopentanol

96-48-02-Ethoxyethyl acetate111-15-9

Dodecane112-40-3Ⅳ໬Ỉ⣲㸦㠀⎔≧㸧ᾮయ༊ศእ㺮㺦㺵㺷㺓㺐㺷

༊ศእ

Methyl isobutyl ketone108-10-1

ࢣࢺࣥ㢮

ᾮయ

༊ศእ

㺮㺦㺵㺷㺓㺐㺷

༊ศእ

n,n-Dimethylguanidine sulfate598-65-2

ᅛయ

༊ศእ

⏕⌮㣗ሷỈ

༊ศእ

↓ᶵ໬ྜ≀
ࣛࢡࢺࣥ㢮㸹
㺫㺡㺹㺙㺐㺖㺶㺍㺖໬ྜ≀࢔ࣝࢥ࣮ࣝ㢮
࢔ࣝࢥ࣮ࣝ㢮㸹
Ⅳ໬Ỉ⣲㸦⎔≧㸧࢔ࣝࢥ࣮ࣝ㢮㸹࢚࣮ࢸࣝ㢮࢔࣑ࢪࣥ㢮㸹◲㯤໬ྜ≀1521

22